It is not clear whether symptoms of tobacco withdrawal are due to lack of nicotine or tobacco. Through the use of denicotinized and nicotinized research cigarettes, we can identify whether symptoms are due to the absence of nicotine or tobacco. Smokers completely abstinent from cigarettes have changes in HPA (hypothalamo-pituitary-adrenal) and HPT (hypothalamo-pituitary-thyroid) axes which parallel withdrawal symptoms, measures of mood, and diminished cognitive performance. Monoamine oxidase (MAO) activities which are reduced in chronic smokers return to normal during tobacco abstinence. Nicotinized cigarettes may prevent these neuroendocrine and MAO changes. Smoking denicotinized cigarettes would not prevent changes related to lack of nicotine, but may continue to inhibit MAO activities thought to be related to some components of smoke. Brain activity that underlies behavioral and cognitive changes related to nicotine exposure may be altered in smokers as a function of state (non-abstinent, abstinent, after abstinence) and as compared to nonsmokers. In this study, we compare the effects of tobacco abstinence or smoking denicotinized research cigarettes to smoking ad libitum nicotinized research cigarettes on the following measures: withdrawal symptoms and quality of sleep;MAO-A and MAO-B activities;hormonal responses (HPA, HPT);mood, cognitive and psychometric performance;functional brain activity, and physiological responses. Research participants are men who are at least 18 years old, report smoking at least 15 cigarettes per day, have not used any illicit drug except marijuana in the past year, have no history of drug or alcohol dependence, and have already experienced tobacco withdrawal symptoms when they had no access to cigarettes. Smokers are randomized into one of 3 groups: a) complete tobacco abstinence for 8 days;b) denicotinized research cigarettes for 8 days, or c) control group smoking nicotinized research cigarettes during the entire study (16 days). Because there are few studies comparing functional brain activity in smokers and nonsmokers, a group of nonsmokers will serve as a control group for the brain imaging studies. Assessments will be performed before, during 8 days of complete abstinence/denicotinized cigarette use, and after subjects resume nicotinized cigarette smoking. Identification of hormonal and MAO changes in association with mood and performance alterations may facilitate the development of new treatments (e.g. thyroid hormones or MAOIs) for smoking cessation. If denicotinized cigarettes can antagonize symptoms of smoking abstinence, they can be developed as a non-nicotinic treatment for tobacco dependence. This study is ongoing, and no results are available yet.